can be used as the basis of environmental decision-making. Combining a fundamental understanding of cellular responses to toxicants with knowledge of tissue dosimetry in cell systems and in exposed human populations will provide a suite of tools to permit more accurate predictions of conditions under which humans are expected to show pathway perturbations by toxicant exposure. The institutional and infrastructural changes required to achieve the committee’s vision will include changes in the types of tests that support toxicity testing and how toxicity, mechanistic information, and epidemiologic data are used in regulatory decision-making. The regulatory transition from the current emphasis on apical end-point toxicity tests to reliance on perturbations of toxicity pathways will raise many issues. The challenges to implementation and a strategy to implement the vision are discussed in Chapter 5.

This chapter discusses individual components of the vision: chemical characterization (component A), toxicity testing (component B), dose-response and extrapolation modeling (component C), population-based and human exposure data (component D), and risk contexts (component E). Component B is composed of a toxicity-pathway component and a limited targeted-testing component. The toxicity-pathway component will be increasingly dominant as more and more high-throughput toxicity-pathway assays are developed and validated. Surveillance and biomonitoring data will be needed to understand the effects of toxicity-pathway perturbations on humans. Finally, the overall success of the new paradigm will depend on ensuring that toxicity testing meets the information needs of environmental decision-making given the risk contexts.


An overview of component A is provided in Figure 3-1. Chemical characterization is meant to address key questions,

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